The Lewis X epitope, Galbeta1-4(Fucalpha1-3)GlcNAc-R, has been implicated in cell-cell recognition events in a number of systems including the central nervous system and is expressed on diverse glycoconjugates including cell adhesion molecules, glycolipids, and the proteoglycan phosphacan. Although Lewis X sequences 3-linked to mannose have been described within proteoglycan fractions of mammalian brain, these have not been reported in other contexts and have been widely believed to be peculiar constituents of brain proteoglycans. In the present paper, we confirm the existence of Lewis X structures O-linked to mannose within the mammalian brain, demonstrate that these structures are present on a well defined mucin-like glycoprotein, cranin (dystroglycan), and report studies suggesting that the linkages involved may be predominantly 2-linked to mannose. Mannose-linked Lewis X is the latest in an increasing list of oligosaccharide recognition "tags" that have been shown to be expressed on cranin (dystroglycan) purified from brain.